1. Monitoring levels of circulating cell‐free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment
- Author
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Dewi Vernerey, Thierry André, Isabelle Trouilloud, Brice Pastor, Thibault Mazard, A.R. Thierry, Cynthia Sanchez, Audrey Bauer, Benoit Roch, Christophe Louvet, Marine Jary, Simon Azan, Christophe Tournigand, Antoine Adenis, Julie Henriques, Gestionnaire, Hal Sorbonne Université, Institut du Cancer de Montpellier (ICM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'Oncologie Médicale [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Cooperator Multidisciplinary Oncology Group (GERCOR), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Henri Mondor, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut mutualiste Monsouris (IMM), Service d'Oncologie Médicale [CHU Saint -Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])
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0301 basic medicine ,Oncology ,Neuroblastoma RAS viral oncogene homolog ,Male ,Cancer Research ,Colorectal cancer ,Pyridines ,[SDV]Life Sciences [q-bio] ,Mutant ,medicine.disease_cause ,chemistry.chemical_compound ,0302 clinical medicine ,Medicine ,Neoplasm Metastasis ,cfDNA ,Research Articles ,RC254-282 ,Regorafenib ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,General Medicine ,Middle Aged ,3. Good health ,[SDV] Life Sciences [q-bio] ,Predictive biomarker ,030220 oncology & carcinogenesis ,Molecular Medicine ,Female ,KRAS ,Colorectal Neoplasms ,Cell-Free Nucleic Acids ,Research Article ,medicine.medical_specialty ,Antineoplastic Agents ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Internal medicine ,Genetics ,Biomarkers, Tumor ,Humans ,In patient ,Mutant ctDNA ,Aged ,business.industry ,Phenylurea Compounds ,Liquid Biopsy ,circulating DNA ,medicine.disease ,Survival Analysis ,Circulating Cell-Free DNA ,030104 developmental biology ,chemistry ,Potential biomarkers ,Tumor response ,business - Abstract
Circulating cell‐free DNA (cfDNA) contains circulating tumor DNA (ctDNA), which can be obtained from serial liquid biopsies to enable tumor genome analysis throughout the course of treatment. We investigated cfDNA and mutant ctDNA as potential biomarkers to predict the best outcomes of regorafenib‐treated metastatic colorectal cancer (mCRC) patients. We analyzed longitudinally collected plasma cfDNA of 43 mCRC patients prospectively enrolled in the phase II TEXCAN trial by IntPlex qPCR. Qualitative (KRAS, NRAS, BRAFV600E mutations) and quantitative (total cfDNA concentration, mutant ctDNA concentration, mutant ctDNA fraction) parameters were correlated with overall survival (OS) and progression‐free survival (PFS). When examined as classes or continuous variables, the concentrations of total cfDNA, mutant ctDNA, and, partly, mutant ctDNA fraction prior to regorafenib treatment correlated with OS. Patients with baseline cfDNA > 26 ng·mL−1 had shorter OS than those with cfDNA value below this threshold (4.0 vs 6.9 months; log‐rank P = 0.0366). Patients with baseline mutant ctDNA > 2 ng·mL−1 had shorter OS than those with mutant ctDNA below this threshold (log‐rank P = 0.0154). We show that pretreatment cfDNA and mutant ctDNA levels may identify mCRC patients that may benefit from regorafenib treatment., Circulating cell‐free DNA (cfdNA) was extracted from longitudinal blood collection of 43 mCRC patients treated by regorafenib. Qualitative (RAS, BRAFV600E mutations) and quantitative (cfDNA concentration, mutant circulating tumor DNA (ctDNA) concentration, mutant ctDNA fraction) parameters were correlated with survival. We show that pretreatment cfDNA and mutant ctDNA levels may identify mCRC patients that may benefit from regorafenib treatment.
- Published
- 2021
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